Systems biology, metabolomics, metabolic engineering, and other recent developments in biochemistry suggest that future biochemists will require a detailed familiarity with the compounds and pathways of intermediary metabolism and their biochemical control. The challenge to the biochemistry instructor is the presentation of metabolic pathways in a manner that allows student creativity in learning the pathways and their components. One approach that does permit the use of problem solving for the study of metabolic pathways involves following the fate of 13 C, 14 C, or 15 N labels, presented originally in the structure of an important metabolic starting compound, through relevant metabolic pathways. This method allows the presentation and study of problems in which such an isotopic label can be traced through two or more metabolic pathways, thus illustrating how these pathways are interconnected. The understanding that all the pathways of intermediary metabolism are interconnected provides opportunities to discuss their metabolic control by such mechanisms as signaling, feedback inhibition, location in organelles, coenzyme levels, and coenzyme recycling rates. The method is illustrated by following the fate of 14 C labels through anaerobic glycolysis, gluconeogenesis, and fatty acid transport, -oxidation, and ketone body formation. Cholesterol biosynthesis and heme formation are used to show that presentations of long and complex pathways can demonstrate important biochemical concepts by following the fate of an isotopic label using only the most important intermediates. Problems based on tracing radioactive labels through one or more metabolic pathways allow the use of cooperative learning techniques.Keywords: Metabolism, metabolic pathways, intermediary metabolism, teaching methods, cooperative learning.In 1972, Joseph Fruton [1] wrote: " . . . One consequence of these successes has been the tendency to describe the present state of the interplay of chemistry and biology largely in terms of the events since 1950. The reasons are various; not the least of them is that the active scientific investigator usually values only the latest work bearing on his own research, the older results already having been woven into the conceptual fabric of his field." Fruton was writing about his colleagues' lack of interest in the historical background of biochemistry, still an accurate observation. Today, his thoughts might be extended to include any area of biochemical research not currently in vogue. In recent years, the biochemistry curriculum at a number of universities has been modified to emphasize fields of current research emphasis, at the expense of areas in which the investigations are not as currently fashionable. The field of intermediary metabolism was one of the areas deemphasized, despite its providing a capstone experience to the students of biochemistry by illustrating how protein conformation, membrane organization, enzyme activities, nucleic acids, metabolic pathways, and biochemical control mechanisms are in...